Piglets are born without the ability to fight disease. Pigs are dependent upon colostrum and later milk from the sow to provide immunoglobulins which confer passive immunity to disease for the first 2 to 3 weeks of life and help “tide them over” until their own immune systems begin functioning. The piglet's endogenous immune system begins to function and produce antibodies in response to environmental stimuli at approximately 2 weeks of age. However, the pig's immune system is not fully competent until about 5 to 6 weeks of age. Until then the pig is susceptible to many biological challenges.
Colostrum contains rapidly diminishing levels of immunologically active, large molecular weight proteins known as immunoglobulins. These immunoglobulins (Ig) possess antibody properties and enhance the pig's immunity to infection by organisms such as bacteria, viruses, and parasites. For various reasons, however, the piglet does not receive adequate amounts of immunoglobulins to impart the necessary immunity. These reasons include problems at lactation, extra large litters, litter competition, poor nursing sows, low birth weight, and sow death. This decreased immunity causes the piglets to become more susceptible to contracting various bacterial, viral, and parasitic infections, which can cause an increase in mortality from diarrhea and dehydration.
In addition to an immature immune system and a deficiency in immunoglobulins, the animals are often affected by environmental and health stress, which also weakens the animals and causes increased susceptibility to disease and various other health problems, including decreased growth and weight gain. Traditionally, these occur during the early growth and weaning period and include stress from the actual weaning process, shipping, heat, social stresses, and various challenges to the animals' health. This weakened condition is often caused by inadequate feed intake and the inability of the animal to assimilate nutritional elements from the intestine. Undigested nutrients will end up in the large intestine as a substrate for undesired intestinal bacteria flora which causes diarrhea in the animal, further complicating the post-weaning performance of the pig.
The mortality from birth to weaning in normal pig production is generally 12 to 15% but can be as high as 20 to 25% in stressed pig populations. Many of these piglets that die are the object of intense care as they are already underweight and under stress after birth. When the young pig is weaned this is an additional stress factor, especially so for the lightest pigs of the litter due to the reasons listed above.
At birth, pigs have limited enzyme systems efficient only for digestion of milk. The amount of lactase, the enzyme that breaks down and digests milk sugar, is high during the first few weeks of life but then decreases shortly after weaning. Meanwhile, proteolytic and amylolytic enzymes needed for grain digestion are not fully developed until 4 to 7 weeks of age. Thus, feed stuffs other than milk cannot be efficiently digested and absorbed until the animal is several weeks old. Further, the stress brought about by abrupt changes in diet and environment are stressful on an animal's digestive system, further aggravating the delicate balance of the system.
Current means for improving growth and reducing post-weaning morbidity in animals include the inclusion of plasma to the animals' diet. Such plasma sources have included spray-dried animal plasma (SDAP). The inclusion of spray-dried animal plasma in the diet improves feed intake, weight gain, and the efficiency of gain when compared to other protein sources such as dried skim milk, whey protein concentrate, soy protein, fishmeal, potato protein, and dried egg products. The immunoglobulin component of SDAP is recognized as the factor that improves growth in weaned pigs.
Spray-dried animal plasma is also utilized commercially in milk replacement products (milk replacers) for pigs, calves and sheep. Milk replacers are typically dry powders containing milk by-products (whey, dried skim milk, whey protein concentrate), soluble, further processed grain products (soy protein concentrate or wheat gluten), fats and oils and appropriate vitamin and mineral fortification. Research has shown that the use of milk replacers fortified with SDAP derived from whey (or colostral whey) results in faster weight gain and reduced morbidity and mortality in calves and pigs. Thomson, D. U., Weaver, Eric M. (1997), “Using Blood Proteins in Calf Milk Replacers,” Large Animal Practice, Vol. 18, No. 6, p. 16. Large Animal Practitioner. The administration of SDAP in milk-replacers has several drawbacks, however.
First, milk replacers which include SDAP are usually provided to pigs or calves through a self-contained feeding system of some type. The feeding systems vary in complexity from a bottle with a nipple to automatic feeding devices. SDAP contains fibrinogen, a water soluble protein, which is activated by very low concentrations of calcium to form fibrin, an insoluble protein matrix. Most sources of tap water contain enough calcium to initiate the activation of the conversion of fibrinogen to fibrin. If the concentration of spray-dried animal plasma in a milk replacement product is high enough and the material is given enough time to form a protein matrix, the resulting gel will plug most feeding devices. While various anticoagulants can be used at high levels to prevent activation of the clotting process, such a level of anticoagulants may have undesirable effects on the animal either by decreasing the availability of beneficial minerals, increasing the osmotic load, or interfering with the blood clotting process in the animal.
Second, milk replacers are expensive and difficult to administer to young pigs, especially those containing significant concentrations of spray-dried animal plasma. Such products are normally prepared between 2-4 times per day in small quantities. Modern swine production is labor-intensive, and these businesses find it difficult to find and keep employees. The addition of labor-intensive production methods, i.e. feeding milk replacement products to the pigs 2-4 times daily, is often not feasible due to the lack of available farm staff.
Further, commercially available milk replacement products usually contain greater than 10% crude fat. This level of fat accumulates and plugs the water lines unless it can be completely removed from the system. Yet another major drawback with milk replacement feeding systems is that the feeding devices must be thoroughly cleaned and disinfected daily to prevent bacterial contamination.
Moreover, although the addition of SDAP to the starter diet of piglets has made it much easier to feed and manage young pigs (less than 21 days of age), it still has not proven to be completely successful in managing the light-end group of pigs, which comprise the bottom 10% of the population. This weight difference at weaning between the heaviest and lightest pigs often leads to greater differences in body weight between the heaviest and lightest pigs at the end of the nursery phase and at slaughter. Such pigs consume very little feed from 0 to 2 days post-weaning. The presence of SDAP in the feed does little to improve the health of the gut in these very small or young pigs since they do not consume adequate concentrations of feed for 2 days post-weaning. The resulting effect in these pigs is temporary gut atrophy, loss of absorptive capacity, an increase in intestinal permeability and bacterial colonization and translocation.
Elliot et al. describe formulations for milk replacement for artificial rearing of neonatal pigs. (U.S. Pat. No. 4,623,541). The formulations include purified immunoglobulins which are subsequently commingled with condensed skim milk and spray dried. The Elliot formulations are problematic, however, since the procedure for separating the immunoglobulins from the blood involves the use of high levels of ammonium sulfate. While ammonium sulfate is satisfactory for small batches of blood, it is not useful for large-scale separation operations due to problems in disposing of this environmentally hazardous compound. In addition, the Elliot process is not economical to use due to its low yields of immunoglobulin powder.
Newson et al. (U.S. Pat. No. 4,096,244) describe the administration of a composition containing active immunoglobulins to newborn piglets by feeding. An important feature of this invention is the reduction of the saline content of the blood serum to increase the palatability of the serum to the pigs. The invention also emphasizes the administration of immunoglobulins to newborn piglets by feeding and describes a feed composition similar to milk replacer. The Newson formulation is not economical to use since it is difficult to administer on a large-scale basis and does not provide for the needs of the newly-weaned pig.
There is therefore a need in the art for a supplement for young pigs (>2 days of age) which is economical and convenient to use on a large scale basis, yet also effective for administration to newly-weaned, underweight pigs.
The present inventors have now synthesized a purified, water-stable immunoglobulin product that can be administered inexpensively through the water supply of animals. The product is highly effective in increasing growth and weight gain in animals.
Accordingly, it is a primary objective of the present invention to provide a composition and method for treating animals using a water-stable, immunoglobulin product based on animal plasma.
It is a further objective of the present invention to provide a composition and method for treating animals which is effective in decreasing the adverse symptoms of stress in young animals, post-weaning.
It is a further objective of the present invention to provide a composition and method for treating animals which increases growth and weight gain.
It is still a further objective of the present invention to provide a composition and method for treating animals which is convenient and economical to administer.
It is still a further objective of the present invention to provide a composition and method for treating animals which is easy and economical to manufacture.
The method and means of accomplishing each of the above objectives as well as others will become apparent from the detailed description of the invention which follows hereafter.